COMPARISON OF THE EFFECTS OF INHALED CORTICOSTEROIDS ON THE AIRWAY RESPONSE TO HISTAMINE, METHACHOLINE, HYPERVENTILATION, AND SULFUR-DIOXIDE IN SUBJECTS WITH ASTHMA

To investigate whether inhaled steroids modulate the airway response to different bronchoconstrictive stimuli, we studied 25 subjects with mild asthma with a double-blind, noncrossover design to compare the effect of a 3-week treatment with salbutamol (0.2 mg, four times a day [q.i.d.]) and placebo (N = 11) to the effect of salbutamol (0.2 mg q.i.d.) and inhaled beclomethasone dipropionate (BDP, 0.5 mg q.i.d.) (N = 14). Airway response to histamine and methacholine was assessed as the provocative concentration (in milligrams per milliliter) necessary to increase the specific airway resistance (SR(aw)) (in centimeters of H2O times second) by 100% (PC100 SR(aw)). Airway response to hyperventilation of air and to hyperventilation of 0.75 ppm of sulfur dioxide (SO2) was determined as the provocative ventilation (in liters per minute) necessary to increase SR(aw) by 75% (PV75 SR(aw)). Challenges were performed on separate days before and after treatment, and salbutamol inhalation was withheld at least 6 hours before each challenge. Salbutamol and placebo did not change prechallenge baseline SR(aw) nor did they have any significant effect on the airway response to the stimuli. Salbutamol and BDP decreased the mean prechallenge baseline SR(aw) (SEM) from 7.7 (0.37) to 5.9 (0.28) (p < 0.01) and significantly (p < 0.01) increased geometric mean (SEM) PC100 SR(aw) for histamine from 0.5 (1.42) to 0.9 (1.53) mg/ml; for metacholine, from 0.2 (1.47) to 0.5 (1.51) mg/ml; and mean (SEM) PV75 SR(aw) for hyperventilation of air from 51.8 (2.32) to 58.4 (1.86) L/min. In contrast, the change of PV75 SR(aw) during hyperventilation of SO2 from 26.2 (2.29) to 31.4 (3.30) L/min was not significant. Our observations confirm previously reported effects of inhaled steroids on metacholine and histamine challenges. However, since BDP had no consistent effect on the SO2 hyperventilation test, we suggest that the efficacy of inhaled steroids depends on the nature of the provoking stimulus.